Journal of Coastal Development ISSN : 1410-5217 Volume 12 Number 1 : 1-12

MARINE BIODISCOVERY RESEARCH IN INDONESIA : CHALLENGES AND REWARDS

Ekowati Chasanah

Research Centre for Marine and Fisheries Product Processing and Biotechnology, Jl. KS Tubun, Petamburan VI, 10260, Indonesia

Received : June, 02, 2008 ; Accepted : August,27,2008

ABSTRACT

Marine biodiscovery or bioprospecting activity is a search for marine products derived from marine biodiversity that can be developed for various industrial needs. Including in this activity is the process of identifying chemical compounds made by biological organisms which is often called natural product discovery. Indonesia, well known as a mega-diversity country, is one of the world hot sport of marine biodiversity. The richness of biodiversity is claimed as mirror of the richness of the chemical compounds, therefore, Indonesian waters might be rewarded with variety of chemical compounds thought to be an endless source of novel drugs and drug leads for pharmaceutical use. Up to 2007, at least 77 new compounds from 14 sponges and 19 new compounds from non-sponge organisms with pharmacological potential have been identified from Indonesian waters. To make this richness potentials becoming real in economic value, many factors should be considered. The bioactive is produced in small quantity, and the lengthy process from discovery step of a novel compound to the preclinical and clinical trials step is usually becoming a problem. Mari culture might be one among methods that can be developed in Indonesia to overcome the degradation hazard of marine resources. Conducive environment for investments, and improvement of technology on marine bioactive production through mariculture are factors to be improved to initiate and develop a sustainable biotechnology industries in Indonesia.

Keywords : marine biodiscovery, Indonesia, pharmacological potential

Correspondence : Phone : +62-21-53650158; +62-21-53650157; email : [email protected]

INTRODUCTION

Humans have been taking advantage of “Drug from the sea” started to boom marine chemical compounds present in after the 1967-symposium in Rhode Island marine organisms for various needs such as University (Fusetani, 2000). Marine natural food sources and disease remedies since products, especially secondary metabolite ancient times. For Indonesian people, compounds, are thought to be an endless chemical compounds present in marine as source of novel drugs and drug leads for well as the terrestrial organisms have pharmaceutical use. Richness of the popularly been used as “jamu”, a traditional chemical compounds in marine environment medicine, through indigenous knowledge generally positively correlated with the passed from one generation to generation richness of biodiversity in the environment since hundreds of years ago. 1 Journal of Coastal Development ISSN : 1410-5217 Volume 12 Number 1 : 1-12

Indonesia is one of the ten countries related Indonesian research institutions as with the richest biodiversity, and is often well as universities. Beginning in 1990, known as a mega-diversity country marine natural product research activities (Anonymous, 2003). In more than 20 years, have been started by Indonesian researchers. Indonesia has become a target for bioactive However, due to some limitations in marine natural product chemistry research, research resources, the progress is not and numbers of novel compounds and significant especially in the form of scientific papers have been published as international scientific papers, patent and cited in the following section. The commercial products. Mostly, biodiscovery uniqueness and richness of biological research activities done in Indonesia is diversity of Asia and Australia and the superficial (i.e preliminary screening transitional zone of the two continents is towards various biological activities), and present in Indonesia. This is supported by more depth activities are usually done in the geological history and topology of foreign country laboratories. Therefore, the Indonesia which is located in the products of invention of advance step such biodiversity path of the Asian continent as structure of novel compounds, including (, , ) and Australia patent of their product and process are () and in the transitional zone of the usually under the properties of foreign- Wallace (, and Nusa researchers. Tenggara Islands). More than 75% of World marine natural products Indonesia’s area is marine with 81,000 km chemistry research, in more than 20 years, of shoreline, the second largest after Canada. has resulted many novel compounds, and This marine biodiversity is considered under some of them have been in the preclinical explored and not fully studied (Anonymous, test for further commercialization, while 2003; de Voogd, 2005). Therefore, some others are already commercialized Indonesian marine biodiversity has become (Faulkner, 2000). More than 2,700 research a target of world and domestic biodiscovery, papers concerning sponges, the most especially marine natural products chemistry secondary metabolite-rich compounds research. among marine organism, have been This review will cover natural published up to year 2000 (Fusateni, 2000). products chemistry research using There are approximately 850 species of Indonesian biota, both by Indonesian as well sponge are believed to be present in as foreign scientists. Organisms, both micro Indonesia (de Voogd & van Soest, 2002), and macro, used in these studies are from and up to 2007, at least 77 new compounds the entire Indonesian marine area, and from 14 sponges and 19 new compounds almost all marine. Sponge, gorgonian and from non-sponge organisms (soft coral, sea soft coral attracted more attention and more pen, octocoral and ascidians) with studied as being well known as rich sources pharmacological potential that will be of novel secondary metabolites. described below.

Sponges

BIODISCOVERY RESEARCH IN The distribution, ecological study as well as INDONESIA sponges bioactivity (based on its brine shrimp, Artemia salina, lethality assay) of

Spermonde archipelago, Sulawesi were Marine biodiscovery research, including studied by de Voogd (2005). From the natural products chemistry, in Indonesia has study, nine (9) sponges were considered been actively conducted by several marine- potential to be developed. The sponge 2 Journal of Coastal Development ISSN : 1410-5217 Volume 12 Number 1 : 1-12

Acanthodendrilla sp. collected from Badi 1999). Further investigation on that sponge Island, Makasar, was investigated by revealed that three (3) new cyclic peptides, William et al. (2004), identifying barangamide B, C and D have been isolated meroterpenoid MAPKAP (MK2) inhibitor. along with four (4) new depsipeptides. Mapkap kinase-2 has important role in the Immunomodulatory test of these compounds regulation of TNF-α production, meaning showed that barangamide A exhibited no that the compound represents a potential immunosuppressive activity up to therapeutic agent to treat inflammatory concentration of 100 µg/mL, while all diseases. Boneratamides A-C, new theonellapeptolides showed mild activity sesquiterpenoids, were isolated from sponge (Roy et al., 2000). Axinyssa aplysinoides from the same Study on sponge Ianthella basta from surrounding Makasar waters (Williams Bay resulted in two (2) more et al. 2004), while a new acyclic bastadins, i.e. bastadin 16 and bastadin 17. diketotriterpenoid has been isolated from Bastadin compounds are well known as Hyrtios erectus sponges, from the inner reef predominantly macrocyclic sponge of Ujung Pandang. This new compound was metabolite compounds (Park et al., 1994). biologically inactive, however, the crude Bobzin et al. (2000) used dereplication extract of the sponge had significant techniques to identify aaptamine from the antimitotic activity (Williams et al., 1999). sponge Aaptos sp. which was harvested From the sponge Stylissa carteri, harvested from Manado, northern Sulawesi, while from the waters in the same area, new Park et al. (1995) studied sponge Lufariella alkaloids latonduines A and B were isolated sp. from the same waters and isolated three by Linington et al. (2003), while two ( 3 ) metabolites, i.e. aaptamine, germacrene (2) new bromopyrrole alkaloids, i.e. alcohol and hexacyclic terpene. The debromostevensine and debromohymenin metabolites showed in vitro activity against were isolated from the same sponge species the KB cancer cell line. From the North collected from Ambon and Sulawesi waters Sulawesi sponge Theonella cf. swinhoei, (Eder et al., 1999). Chemical study of the bitungolides A-F have been isolated. The sponge Leucetta chagosensis from South bitungolides were claimed as a new class of Sulawesi waters found five (5) new Theonella metabolites that are capable of imidazole alkaloids, namely naamine F, inhibiting dual-specificity phosphatase VHR naamine G, kealiinine A, kealiinine B and (Sirirath et al., 2002). A study on a sponge kealiinine C (Hassan et al., 2004). Naamine from Knife cape, Manado Bay, resulted in G showed antifungal activity against seven (7) manzamine type alkaloid Cladosporium herbarum and mild compounds, i.e. two (2) β-carbolines and cytotoxicity against mouse lymphoma and five (5) nucleosides. Among them, five (5) human cervical carcinoma (HeLa) cell lines. new compounds were identified as 32,33- Crude extract of Phyllospongia sp. from dihydro-31-hydroxymanzamine A, 32,33- Makasar’s surrounding waters showed dihydro-6 -dihydroxymanzamine A-35-one, cytotoxicity, and seven (7) new scalarane des-N-methylxestomanzamine A, 32,33- class sesterterpenes have been isolated. All dihydro-6,31-dihydroxymanzamine A and scalaranes isolated exhibited 30-95% 1,2,3,4-tetrahydronorharman-1-one. Most inhibition of KB cells at a concentration of manzamines were active against 10 µg/mL (Roy et al., 2002). From sponge Mycobacterium tuberculosis (H37Rv), Theonella swinhoei, harvested at malaria parasite Plasmodium falciparum and Baranglompo Island, barangamide A, a Leishmania donovani (Rao et al., 2003). In cyclic undecapeptide possessing three N- 1995, an unsymmetrical manzamine dimmer methylated amino acids, and three β- called kauluamine, was isolated from sponge alanines, have been isolated (Roy et al., Prianos sp. harvested from Manado Bay 3 Journal of Coastal Development ISSN : 1410-5217 Volume 12 Number 1 : 1-12

(Ohtani et al., 1995), while Makaluvamine HT-29 and MEL-28 cancer cell lines with G was isolated from the sponge IC50 values of 1µg/mL. Histodermella sp. The compound exhibited Marine sponges harvested from waters significant in vitro cytotoxicity to several surrounding Jakarta showed antimicrobial tumor cell lines and moderate inhibition of activity as well as cytotoxicity. The topoisomerase I, DNA, RNA and protein compounds isolated from the sponge synthesis (Carney et al., 1993). Xestospongia were 4 novel alkaloids of the From waters, four (4) aaptamine class as well as known new polybrominated diphenyl ether aaptamine, isoaaptamine, demethyl (oxy) congeners along with 3 known derivatives aaptamine and its dymethylketal (Calcul et have been isolated from sponge of Dysidea al., 2003). Their antimicrobial activity herbacea Keller (Handayani et al, 1997). towards S. aureus (gram +), E. coli and V. The new polybrominated compounds were angillarum (gram -), and the fungus C. active against a brine shrimp, and all the tropicalis as well as cytotoxicity against compounds isolated were positive against human buccal carcinoma KB was gram positive bacteria Bacillus subtilis and investigated. The results showed aaptamine the phytopathogenic fungus C. 1 and isoaaptamine 2 exhibited antifungal cucumerinum. activity, while significant cytotoxicity A sponge Acanthodendrilla sp. from against KB cells was detected in aaptamine Kundingarengke Island was investigated by 1, isoaaptamine2 and demethyl (oxy) Elkhayat et al. (2004), and 5 new aaptamine 3. Bisdemethylaaptamine, a luffariellolide-related sesterterpenes namely proposed biosynthetic precursor of acantholides A-E, in addition to known aaptamine and bisdemethylaaptamine-9-O- luffrariellolide and its 25-O-methyl and 25- sulfate, has been isolated from the sponge O-ethyl derivatives, have been isolated. The Aaptos sp. from near Bunaken Island, luffariellolide, its 25-O-methyl derivative Manado. This was the first report of a and acantholide E exhibited cytotoxic sulfated aaptamine of bisdemethylaaptamine activity against the mouse lymphoma -9-O-sulfate (Herlt et al., 2004). Meanwhile, L5187Y cell line. Acantholide B, the reddish brown, branching sponge luffariellolide and its 25-O-methyl Echinochalina sp. collected from Derawan derivative were active against Escherichia Island, contained upenamide. This coli, Candida albicans and the pathogenic compound was a new class of macrocyclic fungus Cladosporium herbarum. Twelve marine alkaloid having both new sesterterpenes, honulactones A-L have spirooxaquinolizidinone and hemiaminal been isolated from a lipophilic extract of the ring systems (Jimenez et al., 2000). Two sponge Stresichordaia aliena, family compounds of of 3,6-epidioxy fatty acid, Thorectidae, and further investigation led to monadic acids A and B have been isolated the isolation of 6 new compounds of 20, 24- from an undescribed species of sponge bishomoscalaran sesterterpenes, namely Plakortis sp. These new structural types of honu’enone, phyllofolactones H-K and fatty acids possess both 4-alkyl and 6- phyllofenone C. The sponge was harvested methoxy substituent (Ichiba et al., 1995). from Turtle Bay, Sangkali, Eastern Indonesia waters (Jimenez et al., 2000). Non Sponge (Soft corals, Seapen, Additionally, from the dichloromethane/2- Octacorals, Marine algae) propanol extract of the same organism, 12 new 20,24-bishomoscalaranes, namely From West Sumatera, two new oxygenated honulactones A-L were isolated (Jiminez et sesquiterpenes, i.e. hydroxycolorenone and al., 2000). Honulactones A, B, C and D methoxycolorenone have been isolated from showed cytotoxicity against P-388, A-549, 4 Journal of Coastal Development ISSN : 1410-5217 Volume 12 Number 1 : 1-12

soft coral Nephthea chabrolii (Handayani et compounds have been isolated from the al, 1997). Hydroxycolorenone showed Indonesian ascidian Lissoclinum cf. badium. insecticidal activity against neonate larvae The new compounds have polysulfur of the polyphagus pest insect Spodoptera aromatic amine, and were able to inhibit the littoralis. human promyelocytic leukemia cell line The gorgonian Briareum sp. from HL-60. The effect of 7 compounds on IL-8 Togian Island, near , was production in PMA-stimulated HL-60 cells studied by Rodriguez et al. (1998). revealed the relation of their structures to the They isolated 2 new briarane stecholide IL-8 production activity, the inhibition of diterpenes, namely 2,9 - diacetyl – 2 - cell proliferation and the survival of HL-60 debutyrylstecholide H and 13- cells (Oda et al., 2000). dehydroxystecholide J, with the first A new secosterol compound, along reported cytotoxic activity of the stecholide. with pachyclavulariaenone B, was isolated New briarane diterpenes have been reported from octacoral Pachyclavularia violacea to be isolated from Indonesian sea pen (Anta et al., 2002), from Togian Island. Veretillum malayense, designated as Marine red alga (Rhodophyta) malayenolides A-D. Instead of containing Ceratodictyon spongiosum and its symbiotic acetate and alkanoat groups, this four new sponge Sigmadocia symbiotica harvested diterpenes contains benzoate and senecioate from Biaro Island, have been investigated substituent. This compounds showed for their chemical substances. Two isomers toxicity to brine shrimp with LC50s of <2- of a new and bioactive thiazole-containing 100 ug/mL (Fu et al., 1999). Soft coral cyclic heptapeptide, namely cis,cis- Xenia sp. from Togian Island waters ceratospongamide and trans, trans- produced 2 new xeniolides, i.e. xeniolide –F ceratospongamide have been isolated (Tan and 9-hydroxyxeniolide-F (Anta et al., et al., 2000). The last compound was 2002). All the compounds isolated showed capable of inhibiting the expression of a an IC50 > 1 µg/mL against mouse (P-388) human-sPLA2 promoter-based reporter by and human (A-549, HT-29, MEL-28) tumor 90%, while the first one did not show cell lines. The soft coral Lobophytum sp. activity. collected from a reef wall of Mayu Island, Molluca sea, was studied by Morris et al. Activity of Indonesian Research (1998), and a secosterol with a gorgosterol Institution on Marine Biodiscovery side chain and unusual oxygenation pattern on the A and B rings has been isolated. The A group of scientists from Diponegoro compound, having A and B rings with University, Indonesia, have studied 10 hydroxyl group at C-3 and C-7 and an marine organisms (sponges, gorgonians and epoxide ring at C-5 – C-6, was found active soft corals) from Flores waters, and 5 against human ovarian tumor and human organisms from Jepara, waters. leukemia cell lines. The research found that all crude extracts New tetracyclic pyridoacridine were active on the L-1210 mouse alkaloids have been claimed to be isolated lymphocytic leukemia cell line, giving the from Ujung Pandang waters of ascidian activity value of < 10 mg/L. The most active Eusynstyela latericius (Cropp et al., 1998). compound from gorgonian Isis hippuris was Four compounds, namely styelsamines A-D, identified as gorgosterol derivative (Trianto exhibited mild cytotoxicity against the et al., 2006). human colon tumor cell line HCT-116 with The research group of Sam Ratulangi IC50 values of 33, 89, 2.6 and 1.6 µM, University, Manado have investigated respectively. Three new compounds, sponges, soft corals and algae for lissoclibadins, together with 4 known 5 Journal of Coastal Development ISSN : 1410-5217 Volume 12 Number 1 : 1-12

antibacteria, bio-insecticides, antifeedant based on traditional knowledge with various and other bioactive compounds. Results target screens, i.e. antimicrobial, showed that extracts of sponges bioinsecticide, anticancer, antioxidant, Hymanicidon sp., Placortis nigra, Theonella biopigment, enzymes and their inhibitors, sp., and Placortis nigra, Ianthella sp., and UV protection etc. Antimicrobial soft corals of Sinularia gravis and compounds were extracted from Caulerpa Sarcophyton cinereu had antibacterial racemosa, Sesuvium postulacastrum, activity, while those from Petrosia Xylocarpus granatum, Ulva lactuca. and sea nigricans, Placospongia melobesioides, cucumber Stichopus sp. Antioxidants were Rhabdastrella cf globostellata, Stylissa cf do tained from sea stars Astropecten sp., carteri, Placospongia melobesiodes, Pemphis sp., and Discodoris sp., while Theonella sp., Placospongia melobesioides steroid compounds was detected from were active against Aedes aegypti larvae. Discodoris sp., and Eunice sp. Extracts of Placospongia melobesioides, Research Center for Marine and Acervochalina confusa, Petrosia nigricans Fisheries Product Processing and and Petrosia contignata possesed analgesic Biotechnology, Research of Marine activity. Extracts of sponges of Cinachyra Fisheries Agency has been doing marine sp., Theonella sp., Xestospongia sp., bioprospecting research focusing in both Halichondria, Hoplochalina and primary and secondary metabolites from Perissinella and soft corals Sinularia marine sources for food and non food use. ramosa, S. capillosa, S. procera, S. Enzymes and secondary metabolite compressa, S. gravis, Sarcopyton compounds from seaweed, invertebrates, crassocaule, S. Cinereum and Nephtea sp. fishery-industrial waste, marine derived had the capability of preventing cell microbes have become subjects of the development of sea urchin embryos. natural product discovery research. Extracts Antifeedant activity has been detected in of sponges and soft corals from Binuangen extracts of soft corals of Sinularia (), Seribu Island, Yogyakarta, ovispiculata, S. granosa, S.inexplicita, Karimunjawa, Mataram, South , South Sarcophyton cinereum and extracts of alga Sulawesi (Bonarote and Wakatobi) were Dunaliella sp., Halymenia durvillaei, investigated for the active compounds Laurencia papillosa, Padina australis, against brine shrimp, human cancer cell Liagora sp., Kappaphycus alvarezii, line, antimicrobes and antiangiogenesis. Kappaphycus striatum and Turbinaria Active compounds have been identified decurrens (Mantiri, 2005). as hymeniasidine, stevensine, and Gadjahmada University scientists dibromocantharelline, aaptamine and its screened seaweed, sponge and soft coral isomer isoaaptamine, trigonelline extracts harvested from surrounding and homarine, stelliferin riboside, Yogyakarta waters and Bali against sarcophytoxide, stelletamine, etc, and pathogenic bacteria and fungal, i.e. confirmation of other chemical structure is methicillin resistant S. aureus (MRSA) and in progress. Work in progress is on marine vancomycin-resistant S. aureus (VRSA). A enzyme and secondary metabolites compound identified as Jaspamide has been discovery using metagenomic approach as isolated from Stylissa flabelliformis well as cultivable approach from bacteria (Setyowati et al., 2003; 2004; 2005). The and fungi derived from the sponges. compound exhibited cytotoxicity against myeloma cells with an LC50 of 0.08 g/mL, and active inhibiting Candida albicans. Bogor Agricultural Institute (IPB) scientists did marine biodiscovery research 6 Journal of Coastal Development ISSN : 1410-5217 Volume 12 Number 1 : 1-12

called marine factor. Mariculture is HALLENGES ND C A considered one among methods that can be PRECAUTIONARY EFFORT developed in such Indonesia country. An assessment of mariculture for 6 potential From the papers reviewed, marine sponges, i.e. Aaptos suberitoides, biodiscovery research is strongly needed to Amphimedon paraviridis, Callyspongia gain revenue from the marine resources. (Euplacella) biru, Hyrtios reticulates, Ircina Marine biodiscovery, the first gate of marine ramosa and Pseudoceratina purpurea has biotechnology, offers not only potential been conducted in Spermonde archipelago, benefit in economics through the South Sulawesi (de Voogd, 2005). The study development of biotechnology industries but resulted Callyspongia (E.) blue sponge as also by generating employment. Marine promising candidate due to the high survival bioactive compounds can be developed as rate and significant growth of this species. drugs, industrial enzymes, herbicides, Further trial development of mariculture of cosmetics etc. as their terrestrial Callyspongia (E.) blue showed that survival, counterparts do. It was reported that global growth rates and yield of amphitoxin, the pharmaceutical sales were reported to be active metabolites from this organism, were worth US$550 billion in 2004, and about relatively high (de Voogd, 2005). half of these are made or inspired from Since marine biodiscovery research natural products isolated from nature and its development to biotechnology (Anonymous, 2005). Biodiscovery research industry is very high risk and expensive, is the frontier activity before developing collaboration between research institutions biotechnology industries, and numbers of and industries is obviously needed along benefits can be obtained from this activity, with government support for this activity. such as gaining understanding of marine Local cosmetics and traditional medicine biota and other marine natural industries have used some marine organisms environmental systems. However, as with and plants extracts along with terrestrial other countries’ experience, there is a long plants. Participation of local industries in a way and an expensive cost required to jump biodiscovery-terrestrial plant has initiated, from bioprospecting/biodiscovery research however, their role in marine biodiscovery is into the commercial step of the target very limited. compounds found. It was reported that only A marine-biotechnological industry in 1 compound could be obtained out of 4000- Indonesia has not been developed yet. The 10,000 compounds examined, costing about government and business companies along $ US 1 billion per new drug (Battershill et with researchers have to side by side to al, 2005). develop marine-based biotechnology To bring the active compounds to industries using local materials. Minimizing pharmacies, it needs lengthy process from imported products such as nutraceuticals, discovery step of a novel compounds to the enzymes etc. by producing the products in preclinical and clinical trials. Supply of raw Indonesia will save Indonesian currency. material is a big problem, because direct Favorable environment and government extraction of the compound from marine support for investment should encourage organisms is almost certainly unsustainable. the industry to grow. Intellectual property Concentration of the bioactive is often right and law enforcement system in extremely low, chemical synthesis of the Indonesia is another hindrance of foreign compound may be difficult and costly due to investment involving high technology such its structural complexity, and biosynthesis is as marine biotechnology industries, and the frequently induced by a combination of so system should be improved.

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To strengthen sustainable marine essential in biodiscovery activities. The biodiscovery research activities, the government has updated regulation on how Department of Marine Affairs and Fisheries Indonesian organisms can be accessed by of “Indonesia through Research Agency for foreign researcher, i.e. Government Marine and Fisheries Research and Regulation (PP) no. 41, 2006 by Ministry of Directorate of Marine, Coastal and Small Science and Technology. Collection Islands has initiated founding a scientific protocols of the genetic resources as well as forum called “Indonesian Marine Bio- protocols on benefit sharing by using the pharmaceutical” in July 2005. The resources should be made to follow up the networking among research institutions, regulation. In the past, lack of the regulation universities, government and industries is led to unmanageability of sample access expected to speed up marine biodiscovery especially from the marine environment, activities by sharing the research resources including allowable quantity and sample among the member and encouraging depository. Numbers of Indonesian marine industries to use the technology developed organisms have been deposited at foreign by the researcher. Through this networking, institutes, such as the Netherlands and bargaining position in international research Hawaii museums or foreign universities. collaborations or other activities could be Lack of the protocols led to excessive improved, obtaining better benefit sharing sampling of marine organisms, sometimes in without sacrificing the marine resource. This excessive size, to be taken from their Forum will have a significant role in helping inhabitances. Furthermore, due to limited the government in setting up the sampling equipments for biodiscovery activity in protocols and other technical matters Indonesia, the research is mostly done in regarding sustainable marine biodiscovery foreign countries without proper benefit activities. sharing guided by government. The Government of Indonesia through the Indonesian Ministry of Science and Technology, gave attention to this bioprospecting/biodiscovery activity by CONCLUDING REMARKS developing and building the Bio-island project. The aims of the project include Global commercial interest in marine creating a special economic zone for biodiscovery is increasing. Being mega- biotechnology activity, both research and its biodiversity blessed, Indonesia has an commercialization, in Rempang Island by opportunity to develop marine biodiscovery 2007 (Anonymous, 2003), with focused program, and biotechnology industry for activity on biotechnology of agriculture and their people’s prosperity. However, a lot of food, pharmacology, marine and fisheries, homework is needed to be done to make and industries & environment. Along with biodiscovery activity in Indonesia is in Bio-island, a center of bio prospecting Convention on Biological Diversity (CBD) activities will be built and called Bio park in corridor. The government support and Serpong, West Java. The center, complete encouragement to research institutions and with microbe and other biodiversity biotechnological industries to induce collections as well as a gene bank, will be biodiscovery activities in a sustainable posted as a place for interaction between manner are needed. This include developing industries and bio-prospecting researchers. regulation on the access including However, with unknown reason, the project establishing an efficient and sustainable is stuck without progress. collection of biodiversity, introducing Regulation related with marine benefit sharing, providing support to the organism access and its law enforcement is research center and stimulating biodiscovery 8 Journal of Coastal Development ISSN : 1410-5217 Volume 12 Number 1 : 1-12

research by improving research resources. the ocean depths.Biologist 52 (2) :107- These actions are definitely in urgent need 114 otherwise the blessing of marine mega- biodiversity is lost to foreign prosperity. Bobzin, SC., Yang S. and Kasten TP. 2000. LC-NMR: a new tool to expedite the dereplication and identification of natural products. J. Industrial Microb CKNOWLEDGMENT A Biotechnol (25): 342-345

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Anta C., Gonzalez N., Santafe G., Rodriguez Copp BR., Jompa J., Tahir A., and Ireland J., and Jimenez C. 2002. New Xenia CM. 1998. Stylsamines A-D : new diterpenoids from the Indonesian soft tetracyclic pyridoacridine alkaloids coral Xenia sp. J. Nat. Prod. 65 : 766- from the Indonesian ascidian 768 Eusynstyela latericius. J. Org. Chem. 63 : 8024-8026 Baker DD. 2004 Industrially-held microbial diversity : Are culture collections De Voogd NJ. 2005. Indonesian sponges : really necessary? In Microbial Genetic Biodiversity and mariculture potential. Resources and Biodiscovery. Ed. By PhD thesis, University of Amsterdam, Ipek Kurtboke and Jean Swings. the Netherlands. Queensland Complete Printing Service.269 pp Eder C., Proksch P., Wray V., Steube K., Bringmann G., van Soest RWM., Battershill C., Jaspar M. and Long P. 2005. Sudarsono, Ferdinandus E., Pattisina Marine biodiscovery : new drugs from LA., Wiryowidagdo S. and Moka W. 9 Journal of Coastal Development ISSN : 1410-5217 Volume 12 Number 1 : 1-12

1999. New alkaloids from the Herlt A., Mander L., Rombang W., Indopacific sponge Stylissa carteri. J. Rumampuk R., Soemitro S., Steglich Nat. Prod , 62 : 184-187 W., Tarigan P. And von Nussbaum F. 2004. Alkaloids from marine Elkhayat E., Edrada RA., Ebel R., Wray V., organisms. Part 8 : isolation of van Soest R ., Wiryowidagdo S., bisdemethylaaptine and Mohamed MH, Muller WEG., and bisdemethylaaptine-9-O-sulfate from Proksch. 2004. New Luffariellolide an Indonesian Aaptos sp. marine derivatives from the Indonesian sponge. Tetrahedron 60 : 6101-6104 sponge Acanthodendrilla sp. J. Nat. Prod. 67 : 1809-1817 Ichiba T. and Scheuer PJ. 1995. Two cytotoxic 3,6-epidioxy fatty acids Faulkner DJ,. 2002. Marine Natural from an Indonesian sponge, Plakortis Products. Nat. Prod. Rep. 19: 1-48 sp. Tetrahedron 51 (45) : 12195- 12202 Fusetani N. 2000. Drugs from the sea. Karger. 158 pp. Jimenez JI., Goetz G., Mau CMS, Yoshida WY., Scheuer PJ., Williamson RT., Fu X., Schmitz FJ., and Williams GC. 1999. and Kelly M. 2000. Upenamide : an Malayenoldes A-D, novel diterpenes unprecedented macrocyclic alkaloid from the Indonesian sea pen from the Indonesian sponge Veretillum malayense. J. Nat. Prod. Echinochalina sp. J. Org. Chem. 65 : 62 : 584-586 8465-8469

Handayani D., Edrada RA., Proksch P., Jimenez JI., Yoshida WY., Scheuer PJ., and Wray V., Witte L., Van Soest RWM., Kelly M. 2000. Scalarane-based Kunzmann A., and Soedarsono. 1997. sesterterpenes from an Indonesian Four new bioactive polybrominated sponge Strepsichordaia aliena. J. Nat. diphenyl ethers of the sponge Dysidea Prod. 63 :1388-1392 herbacea from west Sumatra, Indonesia. J. Nat. Prod. 60 : 1313- Jimenez JI., Yoshida WY., Scheuer PJ., 1316 Lobkovsky E., Clardy J. and Kelly M. 2000. Honulactones : New Handayani D., Edrada RA., Proksch P., bishomoscalarane sesterterpenes from Wray V., Witte L., Van Soest RWM., the Indonesian sponge Stresichordaia Van Ofwegen L., and Kunzmann A.. aliena. J. Org. Chem. 65 : 6837-6840 1997. New oxygenated sesquiterpenes from the Indonesian soft coral Kobayashi M. 2000. Search for biologically Nephthea chabrolii . J. Nat. Prod. 60 : active substance from marine sponges 1313-1316 In Drugs from the Sea. Edited by N. Fusatani. Karger. 158 pp Hassan W., Edrada RA., Ebel R., Wray V., Berg A., van Soest R, Wiryowidagdo Kurtboke DI. Uniqueness of the “Smart S. And Proksch P. 2004. New State’s” microbial diversity. In Imidazole alkaloids from the Microbial genetics resources and Indonesian sponge Leucetta biodiscovery. Ed. by Ipek Kurtboke chagosensis. J. Nat. Prod. 67 : 817- and Jean Swings.2004. Queensland 22. Complete Printing Service. 269pp

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Linington RG., Williams DE., Tahir A., van Luffariella sp. Korean Chemical Soest R., and Andersen RJ. 2003. Society 39 (7) : 559-563 Latonduines A and B, new alkaloids isolated from the marine sponge Pramono E. 2002. The commercial use of Stylissa carteri : Structure elucidation, traditional knowledge and medicine sysnthesis, and biogenic implications. plants in Indonesia. Presented at Organic Letters 5 (15) : 2735-2738 Multi-stakehoder dialogue on trade, intellectual property right and Mantiri D. 2005. Present status of Marine biological resources in Asia. and fisheries research on bio- Bangladesh, April 19-21 pharmaceutical at Sam Ratulangi University. Proceeding of Marine and Rao KV., Santarsiero BD., Mesecar AD., Fisheries Bio-pharmaceutical. Schinazi RF., Tekwani BL., and Research Agency for Marine and Hamann MT. 2003. New manzamine Fisheries, Jakarta. (Indonesian): 203pp alkaloids with activity against infectious and tropical parasitic Morris LA., Christie EM., Jaspars M., and diseases from an Indonesian sponge. van Ofwegen L. 1998. A bioactive J. Nat. Prod. 66 : 823-828 secosterol with unusual A- and B-ring oxygenation pattern isolated from an Rodriguez J., Nieto RM and Jimenez. 1998. Indonesian soft coral Lobophytum sp. New briarane stecholide diterpenes J. Nat. Prod. 61 : 538-541 from the Indonesian gorgonian Briareum sp. J. Nat. Prod. 61 (3) Oda T., Fujiwara T., Liu H., Ukai K., Mangindaan REP., Mochizuki M., and Roy, MC., Tanaka J., de Voogd N., and Namikoshi M. 2006. Effects of Higa T. 2002. New scalarane class lissoclibadines and lissoclinotoxins, sesterterpenes from an Indonesia isolated from a tropical ascidian sponge, Phyllospongia sp. J. Nat. Lissoclinum cf. badium, on IL-8 Prod. 65 : 1838-1842 production in a PMA-stimulated promyelocytic leukemia cell line. Roy MC., Ohtani I I., Tanaka J., Higa T. Marine Drugs 4 : 15-21 And Satari R. 1999. Barangamide A, a new cyclicpeptide from the Indonesian Ohtani I I., Ichiba T., Isobe M., Kelly- sponge Theonella swinhoei. Borges M., and Scheuer PJ. 1995. Tetrahedron Letters 40 : 5373-5376 Kauluamine : an unprecedebted manzamine dimmer from an Roy MC., Ohtani I I., Ichiba T., Tanaka J., Indonesian marine sponge Prianos sp. Satari R. And Higa T. 2000. New J. Am. Soc. 117 : 10743-10744 cyclic pepteides from the Indoensian sponge Theonella swinhoei. Park SK., Jurek J., Carney JR., and Scheuer Tetrahedron Letters 56 : 9079-9092 PJ. 1994. Two more bastadin, 16 and 17, from an Indonesian sponge Sirirath S., Tanaka J., Ohtani I I., Ichiba T., Ianthella basta. J. Nat. Prod. 57 (3) Rachmat R., Ueda K., Usui T., Osada 407-410 H., and Higa T. 2002. Bitungolides A- F, new polyketides from the Park, SK., Kim SS., Hong JS and Kim IK. Indonesian sponge Theonella 1995. A study on the chemical swinhoei. J. Nat. Prod. 65 : 1820-1823 constituents from marine sponge 11 Journal of Coastal Development ISSN : 1410-5217 Volume 12 Number 1 : 1-12

Setyowati, E.P., Sudarsono, S. Wahyuono. Triatno. 2006. Present status of marine and 2003. Active fraction from sponge fisheries research on bio- Stylissa flabelliformis collected pharmaceutical at Diponegoro from Menjangan National Park University. Proceeding of Marine and West Bali, Technoscience. 16(3): fisheries bio-pharmaceutical. Research 499-513. Agency for Marine and Fisheries, Jakarta. (Indonesian): 203pp Setyowati, E.P., Sudarsono, S. Wahyuono. 2004. Cytotoxic and antimicrobial Williams DE., Tahir A., and Andersen test of the bioactive compound RJ. 1999. A new acyclic isolated from Stylissa flabelliformis diketotriterpenoid isolated from the sponge. Indonesian Journal Indonesian marine sponge Hyrtios Pharmacy. 15(2): 50-56. erectus. J. Nat. Prod., 62: 653-654

Setyowati, E.P., Sudarsono, S. Wahyuono. Williams, DE., Patrick BO., Tahir A., van 2005. Jaspamide: structure Soest R., Roberge M.. and Andersen identification of citotoxic and RJ. 2004. Boneratamides A-C, new fungicide compound from Stylissa sesquiterpenoids isolated from the flabelliformis Sponges. Indonesian marine sponge Axinyssa aplysinoides. Journal Pharmacy. 16(1): 67-73. J. Nat. Prod, 67 : 2127-2129. J. Nat. Prod., 67 : 1752-1754 Tan LT., Williamson T. and Gerwick WH. 2000. Cis, cis- and trans, trans- Williams, DE., Telliez JB, Liu J., Tahir A., ceratospongamide, new bioactive van Soest R. and Andersen RJ. 2004. cyclic heptapeptides from the Meroterpenoid MAPKAP (MK2) Indonesia red alga Ceratodictyon inhibitors isolated from the Indonesian spongiosum and symbiotic sponge marine sponge Acanthodendrilla sp. J. Sigmadocia symbiotica. J. Org. Chem. Nat. Prod, 67 : 2127-2129 65 : 419-425.

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